Microencapsulation of human growth hormone within biodegradable polyester microspheres: Protein aggregation stability and incomplete release mechanism

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Recombinant human growth hormone (rhGH) was encapsulated within poly(D,L-lactic-co-glycolic acid) microspheres by a double emulsion solvent evaporation method. A mixture of methylene chloride and ethyl acetate in varying volume ratios was used for the microsphere preparation. Protein release profiles from three different microsphere formulations demonstrated initial burst effects ranging from 28.2% to 54.7% after a 1-day incubation and exhibited no further significant releases up to 19 days. This was because the encapsulated rhGH with the microspheres was largely aggregated in a noncovalent fashion du ring the formulation. Nonaggregated water soluble rhGH species within the microspheres are likely to be responsible for the rapid release upon incubation. The initially released rhGH in the incubation medium, however, was composed of mostly monomer species with a small amount of dimer as probed by size-exclusion chromatography. Circular dichroism spectra of the initially released rhGH in the medium revealed that the conformation of the released rhGH was correctly folded relative to that of native rhGH, with little variation in alpha-helix contents depending on the formulations. The "nonrelease" mechanism after the initial burst release was attributed to nonspontaneously dissociable noncovalent protein aggregation and surface adsorption of rhGH present within the microspheres. (C) 1999 John Wiley & Sons, Inc.
Publisher
JOHN WILEY & SONS INC
Issue Date
1999
Language
English
Article Type
Article
Keywords

GLYCOLIC ACID) MICROSPHERES; AIR-LIQUID INTERFACE; CIRCULAR-DICHROISM; STABILIZATION; DENATURATION; FORMULATIONS; DEGRADATION; SHEAR; FORM

Citation

BIOTECHNOLOGY AND BIOENGINEERING, v.65, no.6, pp.659 - 667

ISSN
0006-3592
DOI
10.1002/(SICI)1097-0290(19991220)65:6<659::AID-BIT6>3.0.CO;2-9
URI
http://hdl.handle.net/10203/11043
Appears in Collection
BS-Journal Papers(저널논문)
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